The current project has been investigating a method that dramatically ameliorates age-related hearing loss in several inbred strains of mice that serve as models for presbycusis and other forms of progressive sensorineural hearing loss. The treatment involves an augmented acoustic environment (AAE), an extended period of nontraumatic acoustic stimulation for 12 hours each day. Positive effects of AAE treatment include slowing progressive elevation of auditory brainstem response (ABR) thresholds, diminished loss of outer hair cells and spiral ganglion cells, lessened age-related reduction of volume and neuron loss in the anterior ventral cochlear nucleus (AVCN), increased amplitude of the acoustic startle response, and stronger prepulse inhibition (PPI; indicative of the behavioral salience of sounds). However, in demonstrating these findings, the current project has revealed that the effects of AAE treatment are complicated by several factors including sex, frequency spectrum of the AAE; and age or degree of progressive hearing loss at initiation of AAE treatment. The continuation project addresses these factors, focusing on histopathology of the cochlea and AVCN using D2 and B6 mice. Aim 1 will evaluate an observed sex effect in B6 mice: females between about 6-12 months of age (when fertility and estrogen are declining) exhibk an acceleration in the rate and severity of hearing loss compared to males. Findings stemming from this aim can help us to better understand sexrelated factors that may modulate presbycusis in humans. Aim 2 will elucidate variables respons_le for the positive effects of AAE treatment on cochlear tissue using histological methods. The goal is to gain additional insight into mechanisms associated with AAE effects. Aim 3 will study the role of sex hormones and other variables involved in central AAE effects, including the death in AVCN neurons in AAE-treated male B6 mice and neuron protection observed in females. The findings will have implications with respect to possible effects of the acoustic environment (e.g.,arnplification) on the central auditory system. Aim 4 will evaluate in greater detail the effects of very early initiation of AAE treatment, which has potential clinical implications. The proposed continuation project can help us to better understand progressive sensorineural hearing loss and factors that modulate it, such as sex hormones and age at intervention. The ultimate goal is to develop new approaches for amelioration and treatment ofpresbycusis and other hearing disorders. [unreadable] [unreadable]